New Concise and Efficient Synthesis of Rubrolides C and E via Intramolecular Wittig Reaction by Nilesh P. Tale, Amol V. Shelke, Girdharilal B. Tiwari, Prerana B. Thorat, and Nandkishor N. Karade* Department of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra 440 033, India (e-mail: nnkarade@gmail.com) A short total synthesis of rubrolides C and E has been achieved in four steps, using readily available 4-methoxyacetophenone, 2-bromoacetic acid, and the appropriate aromatic aldehyde, in 46 and 45% yield, respectively. Key reactions involved are a-tosyloxylation of the aryl methyl ketone, intramolecular Wittig reaction, Knoevenagel condensation, and demethylation. Introduction. – The g-benzylidenebutenolide motif with two 4-hydroxyphenyl moieties, with or without halogen atoms, is a common structural feature of a novel family of biologically active marine ascidian metabolites called rubrolides ( Fig. ) [1]. The rubrolides without halogen atoms at C(3) of the butenolide framework are A, C, D, E, and J. The presence of a Cl-atom at C(3) of the furan-2(5H)-one is found in the rubrolides B, I, K, L, M, and O, while 3-Br substitution occurs in rubrolide N only. Rubrolides A to H were isolated in 1991 from the colonial tunicate Ritterella rubra. It is noteworthy that only minute amounts of rubrolide A (132 mg) , B (68 mg), C (48 mg) , D (4 mg), E (3 mg), G (8 mg), and H (11 mg) could be obtained from 400 g of the frozen specimens of Ritterella rubra after multiple purification steps. The rubrolides are potent non-nitrogenous antibiotics and were also found to possess moderate but selective inhibition of protein phosphatases 1 and 2A. Rubrolides I, K, L, and M have been isolated from the red colonial tunicate Synoicum blochmanni and found to display significant cytotoxicities against four different cancer cells lines [2]. Moreover, rubrolide L has recently been shown to be a potent inhibitor of human aldose Helvetica Chimica Acta – Vol. 95 (2012) 852  2012 Verlag Helvetica Chimica Acta AG, Zürich Figure. Naturally occuring bioactive rubrolides